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INOVATYON STUDY -International, Randomized Study in Patients With Ovarian Cancer (INOVATYON)

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ClinicalTrials.gov Identifier: NCT01379989
Recruitment Status : Active, not recruiting
First Posted : June 23, 2011
Last Update Posted : July 18, 2018
Sponsor:
Collaborators:
PharmaMar
Averion International Corporation
Information provided by (Responsible Party):
Mario Negri Institute for Pharmacological Research

Brief Summary:
The objective of this multicentric, randomised, Phase III study is to demonstrate superiority, in terms of survival, of trabectedin and Pegylated Liposomal Doxorubicin (PLD) versus carboplatin and PLD in partially-platinum sensitive ovarian cancer patients.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Drug: Carboplatin Drug: Pegylated Lipoxomal Doxorubicin (PLD) Drug: Trabectedin Phase 3

Detailed Description:

Patients will be randomised to:

Arm A: PLD 30 mg/m2 and carboplatin AUC 5; Arm B: PLD 30 mg/m2 and trabectedin 1.1 mg/m2. Patients' characteristics: patients over 18 years of age with advanced, progressive ovarian cancer 6-12 months after completion of first line or second line treatment with platinum-based chemotherapy.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 588 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase III International, Randomized Study of Trabectedin Plus Pegylated Liposomal Doxorubicin (PLD) Versus Carboplatin Plus PLD in Patients With Ovarian Cancer Progressing Within 6-12 Months of Last Platinum
Study Start Date : June 2011
Estimated Primary Completion Date : July 2020
Estimated Study Completion Date : July 2020


Arm Intervention/treatment
Active Comparator: Carboplatin plus PLD
Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/ m2 followed by carboplatin AUC 5.
Drug: Carboplatin
Carboplatin AUC 5
Other Name: Carboplatin generic

Drug: Pegylated Lipoxomal Doxorubicin (PLD)
PLD 30 mg/m² i.v.
Other Name: Caelyx

Experimental: Trabectedin plus PLD
Pegylated Lipoxomal Doxorubicin (PLD) 30 mg/m2 infusion followed by trabectedin 1.1 mg/m2 infusion.
Drug: Pegylated Lipoxomal Doxorubicin (PLD)
PLD 30 mg/m² i.v.
Other Name: Caelyx

Drug: Trabectedin
trabectedin 1.1 mg/m2 3-hour i.v. infusion on Day 1 every 3 weeks. The use of central venous access is strongly recommended.
Other Name: Yondelis




Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled ]
    This is an event driven study. The study will continue until 442 events have occurred.


Secondary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    PFS will be measured from the date of randomization to the date of documented PD or death (regardless of cause of death).

  2. Objective RR [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Objective RR will be the best response obtained in any evaluation according to RECIST 1.1

  3. CA-125 serological response [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    CA-125 serological response will be the best response obtained in each arm

  4. Duration of Response [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Duration of response: will be calculated from the date of first documentation of response (CR or partial response [PR], whichever occurs first) to the date of documented PD or death.

  5. Time to subsequent chemotherapy administration [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    The time from randomization to subsequent chemotherapy counted from the administration of subsequent chemotherapy will be evaluated as an exploratory analysis.

  6. OS for Subsequent chemotherapies [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    the overall survival counted from the administration of subsequent chemotherapy until death

  7. PFS for the Subsequent Chemotherapies [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    the progression free survival counted from the administration of subsequent chemotherapy untill disease progression or death whichever occurs first

  8. Frequency of serious adverse events (SAEs) [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Number of SAEs for each randomization arm

  9. QoL according to the EORTC QLQ-C30 and QLQ-OV28 [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Two PRO instruments will be administered in this study: the EORTC QLQ-C30 and QLQ-OV28.PRO instruments will be completed by the patient at screening (before randomization) and within four weeks after the 6th cycle or at the time of progression, whichever occurs first.

  10. Best response to each Subsequent chemotherapy line [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    The best response obtained to each Subsequent chemotherapy line calculated as frequency of patients with CR, PR, SD or PD.

  11. Frequency of toxicities, graded according to the NCI-CTAE version 4.0 [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Clinical and laboratory toxicities

  12. Frequency of toxicities leading to dose delays [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Clinical and laboratory toxicities

  13. Frequency of toxicities leading to dose modifications [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Clinical and laboratory toxicities

  14. Frequency of toxicities leading to treatment discontinuation [ Time Frame: This outcome measure will be assess approximately 4.5-5 years after the last patient enrolled, at the same time points of the Primary Endpoint ]
    Clinical and laboratory toxicities



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Female, aged ≥ 18 years
  2. Histologically and/or cytologically proven epithelial ovarian, epithelial fallopian tube cancer or primary peritoneal cancer
  3. Progression free interval between six and twelve (6-12) months (calculated from the first day of the last cycle of the last platinum-based chemotherapy until the date of progression confirmation through radiologic imagery). Patients may have received up to two platinum-based chemotherapy lines, of which at least one must have contained a taxane
  4. Measurable or evaluable disease confirmed by radiological imaging, such as magnetic resonance imaging (MRI), computed tomography (CT) scan, or PET/CT scan at study entry (CA-125 rise not supported by radiological evidence of disease is not accepted as criteria for defining progression) or histological proven recurrent ovarian cancer even in the absence of postoperatively measurable or evaluable lesions.
  5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2
  6. Estimated life expectancy ≥ 12 weeks
  7. Patients must be accessible for treatment and follow-up
  8. Adequate organ function within 14 days prior to first cycle as evidenced
  9. Patients must be able to receive dexamethasone or its equivalent, which is required if randomly assigned to treatment with trabectedin plus PLD
  10. Informed consent of the patient

Exclusion Criteria:

  1. Non epithelial ovarian or mixed epithelial/non epithelial tumors (e.g., Mullerian tumors)
  2. Patients who did not respond to last platinum-based therapy or in whom last relapse occurred < 6 months or > 12 months from the last dose of platinum
  3. Bowel obstruction, sub-occlusive disease or the presence of symptomatic brain metastases
  4. Pre-existing grade > 1 motor or sensory neuropathy according to the National Cancer Institute Common Toxicity Criteria Adverse Event (NCI-CTCAE) version 4.0
  5. Myocardial infarct within six months before enrolment, New York Association (NYHA) Class II or worse heart failure (Appendix 1. The New York Heart Association), uncontrolled angina, severe uncontrolled ventricular arrythmias, clinically significant pericardial disease, or electrocardiographic evidence of acute ischemic or active conduction system abnormalities
  6. History of liver disease
  7. Concurrent severe medical problems or any unstable medical condition unrelated to malignancy, which would significantly limit full compliance with the study or expose the patient to extreme risk or decreased life expectancy
  8. Breastfeeding women and women of child bearing potential must use effective contraception during treatment and 3 months thereafter, which may include prescription contraceptives (oral, injection, or patch), intrauterine device, double-barrier method or male partner sterilization (not applicable to patients that are surgically sterile)
  9. Prior exposure to trabectedin
  10. Prior resistance to anthracyclines or PLD defined as a progression during anthracycline-based chemotherapy or a recurrence within 6 months from its ending
  11. Prior severe PLD related toxicity
  12. Prior exposure to cumulative doses of doxorubicin >400mg/m2 or epirubicin >720mg/m2
  13. Treatment with any investigational product within 30 days prior to inclusion in the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01379989


  Show 132 Study Locations
Sponsors and Collaborators
Mario Negri Institute for Pharmacological Research
PharmaMar
Averion International Corporation
Investigators
Principal Investigator: Nicoletta Colombo, MD European Institute of Oncology (I.E.O), Milan, Italy

Responsible Party: Mario Negri Institute for Pharmacological Research
ClinicalTrials.gov Identifier: NCT01379989     History of Changes
Other Study ID Numbers: ET-D-009-10
First Posted: June 23, 2011    Key Record Dates
Last Update Posted: July 18, 2018
Last Verified: July 2018

Additional relevant MeSH terms:
Ovarian Neoplasms
Neoplasms, Glandular and Epithelial
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Neoplasms by Histologic Type
Liposomal doxorubicin
Trabectedin
Carboplatin
Doxorubicin
Antineoplastic Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents